Master of Science
Prenatal cannabis exposure (PCE) has been implicated in the increased incidence of several neuropsychiatric disorders, including autism spectrum disorder (ASD). Due to the ongoing rise in cannabis usage, the present thesis investigated the effect of tetrahydrocannabinol (THC), the psychoactive constituent of cannabis, on a rat model of ASD. Male and Female Sprague-Dawley offspring were prenatally exposed to saline or THC from gestational day (GD)6 until GD21. Sensorimotor processing and gating, an aspect commonly disrupted in ASD, was assessed via the acoustic startle reflex (ASR), prepulse inhibition (PPI), and gap-prepulse inhibition (Gap-PPI). THC-exposed offspring exhibited a higher threshold, and a higher half-maximal response (ES50) for the ASR. Moreover, THC-exposed offspring showed higher PPI but no change in Gap-PPI. These findings indicated a lowered startle reactivity and heightened PPI. This thesis presents contrasting PPI data to previous neuropsychiatric models, building the foundation to better understand the sensitivity of model validity and the impact of prenatal THC exposure on a non-human model.
Summary for Lay Audience
With the recent federal legalization of cannabis products within Canada, there is a steady rise in cannabis consumption across the nation’s younger cohorts. Particularly, younger pregnant women have seen the greatest rise in cannabis use during their pregnancy term. This is due to the misconception that cannabis is a natural remedy for pregnancy challenges, including morning sickness. Several large-scale population studies within Canada have begun to show an increased prevalence of neuropsychiatric disorders, namely autism spectrum disorder (ASD),potentially due to prenatal cannabis exposure (PCE). To understand the cause of these population trends, we administered THC, the psychoactive compound found in cannabis, to pregnant rats for the length of the pregnancy. To appreciate the relationship between PCE and neuropsychiatric disorders, we investigated a core mechanism of sensory filtering that is affected in ASD. The offspring of the injected dams were used to investigate PCEs effect on the rat’s physical reaction to loud auditory noises. We further looked at how the rats filter sound by administering quieter preceding auditory cues directly before the loud noise and measured the effect on the physical reaction. The present thesis found that rats exposed to THC needed louder noise pulses to physically react and had strengthened auditory filtering. This contradicts several other papers that show a deficiency in appropriate filtering in PCE models. These findings help drive the discussion forward on the importance of model validity, and the sensitivity of the parameters used to run the behavioral paradigm.
Maroon, Melvin, "The Effect of Prenatal THC Exposure on ASD-Relevant Sensorimotor Behaviour in Rats" (2023). Electronic Thesis and Dissertation Repository. 9879.
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